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Background/Objectives: The incidence and prevalence of tricuspid regurgitation (TR) are increasing worldwide. "Traditional" drug therapy with diuretics is often ineffective and the identification of new strategies, including non-pharmacological ones, is an urgent need. The aim of this study was to summarize the results on the efficacy and safety of Cardioband, one of the few approved transcatheter tricuspid valve repair systems, in patients with TR. Methods: Three databases (Medline, Scopus, and CENTRAL) were searched to identify clinical trials and observational studies on the efficacy (primary outcome) and safety (secondary outcome) of Cardioband. A random-effects meta-analysis was performed with R software (version 4.3.3). Survival and freedom from heart failure (HF) hospitalization were estimated with the method of reconstructing individual patient data from Kaplan–Meier curves (IPDfromKM). Results: Eleven studies were included in this systematic review and meta-analysis. Cardioband significantly reduced annulus diameter (−9.31 mm [95% Confidence Interval, CI: −11.47; −7.15]), vena contracta (−6.41 mm [95% CI: −8.34; −4.49]), and effective regurgitant orifice area (EROA) (−0.50 cm2 [95% CI: −0.72; −0.28]) in patients with TR. Cardioband reduced the severity of TR and the extent of heart failure in 91% [95% CI: 85; 97] and 63% [95% CI: 52–75] of patients, respectively. Finally, Cardioband implantation was associated with prolonged survival and freedom from HF hospitalization (80.1% and 57.8% at 24 months, respectively). Conclusions: This study demonstrates that Cardioband implantation leads to cardiac remodeling and mechanical improvements, reduces the severity of TR, and improves quality of life. Therefore, Cardioband is an effective option for the non-pharmacological treatment of TR. [ABSTRACT FROM AUTHOR]

The prevalence of overweight and obesity has progressively increased in the last few years, becoming a real threat to healthcare systems. To date, the clinical management of body weight gain is an unmet medical need, as there are few approved anti‐obesity drugs and most require an extensive monitoring and vigilance due to risk of adverse effects and poor patient adherence/persistence. Growing evidence has shown that the gasotransmitter hydrogen sulfide (H2S) and, therefore, H2S‐donors could have a central role in the prevention and treatment of overweight/obesity. The main natural sources of H2S‐donors are plants from the Alliaceae (garlic and onion), Brassicaceae (e.g., broccoli, cabbage, and wasabi), and Moringaceae botanical families. In particular, polysulfides and isothiocyanates, which slowly release H2S, derive from the hydrolysis of alliin from Alliaceae and glucosinolates from Brassicaceae/Moringaceae, respectively. In this review, we describe the emerging role of endogenous H2S in regulating adipose tissue function and the potential efficacy of natural H2S‐donors in animal models of overweight/obesity, with a final focus on the preliminary results from clinical trials. We conclude that organosulfur‐containing plants and their extracts could be used before or in combination with conventional anti‐obesity agents to improve treatment efficacy and reduce inflammation in obesogenic conditions. However, further high‐quality studies are needed to firmly establish their clinical efficacy. [ABSTRACT FROM AUTHOR]

Metformin (Met) is the first-line therapy in type 2 diabetes mellitus but, in last few years, it has also been evaluated as anti-cancer agent. Several pathways, such as AMPK or PI3K/Akt/mTOR, are likely to be involved in the anti-cancer Met activity. In addition, hydrogen sulfide (H2S) and H2S donors have been described as anti-cancer agents affecting cell-cycle and inducing apoptosis. Among H2S donors, isothiocyanates are endowed with a further anti-cancer mechanism: the inhibition of the histone deacetylase enzymes. On this basis, a hybrid molecule (Met-ITC) obtained through the addition of an isothiocyanate moiety to the Met molecule was designed and its ability to release Met has been demonstrated. Met-ITC exhibited more efficacy and potency than Met in inhibiting cancer cells (AsPC-1, MIA PaCa-2, MCF-7) viability and it was less effective on non-tumorigenic cells (MCF 10-A). The ability of Met-ITC to release H2S has been recorded both in cell-free and in cancer cells assays. Finally, its ability to affect the cell cycle and to induce both early and late apoptosis has been demonstrated on the most sensitive cell line (MCF-7). These results confirmed that Met-ITC is a new hybrid molecule endowed with potential anti-cancer properties derived both from Met and H2S. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is an endogenous gasotransmitter that promotes multiple biological effects in many organs and tissues. An imbalanced biosynthesis of H2S has been observed in animal models of age-related pathological conditions. However, the results from human studies are inconsistent. We performed a systematic review with meta-analysis of studies searched in Medline, Embase, Scopus, and CENTRAL databases. We included observational studies on patients with age-related diseases showing levels of H2S in blood, plasma, or serum. All the analyses were carried out with R software. 31 studies were included in the systematic review and 21 in the meta-analysis. The circulating levels of H2S were significantly reduced in patients with progressive, chronic, and degenerative diseases compared with healthy people (standardized mean difference, SMD: −1.25; 95% confidence interval, CI: −1.98; −0.52). When we stratified results by type of disorder, we observed a significant reduction in circulating levels of H2S in patients with vascular disease (e.g., hypertension) (SMD: −1.32; 95% CI: −2.43; −0.22) or kidney disease (SMD: −2.24; 95% CI: −4.40; −0.08) compared with the control group. These results could support the potential use of compounds targeting the "H2S system" to slow down the progression of many diseases in the elderly. [ABSTRACT FROM AUTHOR]

Vascular inflammation (VI) represents a pathological condition that progressively affects the integrity and functionality of the vascular wall, thus leading to endothelial dysfunction and the onset of several cardiovascular diseases. Therefore, the research of novel compounds able to prevent VI represents a compelling need. In this study, we tested erucin, the natural isothiocyanate H2S-donor derived from Eruca sativa Mill. (Brassicaceae), in an in vivo mouse model of lipopolysaccharide (LPS)-induced peritonitis, where it significantly reduced the amount of emigrated CD11b positive neutrophils. We then evaluated the anti-inflammatory effects of erucin in LPS-challenged human umbilical vein endothelial cells (HUVECs). The pre-incubation of erucin, before LPS treatment (1, 6, 24 h), significantly preserved cell viability and prevented the increase of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) levels. Moreover, erucin downregulated endothelial hyperpermeability and reduced the loss of vascular endothelial (VE)-Cadherin levels. In addition, erucin decreased vascular cell adhesion molecule 1 (VCAM-1), cyclooxygenase-2 (COX-2) and microsomal prostaglandin E-synthase 1 (mPGES-1) expression. Of note, erucin induced eNOS phosphorylation and counteracted LPS-mediated NF-κB nuclear translocation, an effect that was partially abolished in the presence of the eNOS inhibitor L-NAME. Therefore, erucin can control endothelial function through biochemical and genomic positive effects against VI. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H2S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H2S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H2S donors. The H2S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H2S by antiglaucoma H2S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds. [ABSTRACT FROM AUTHOR]

After the discovery of hydrogen sulfide (H2S) in the central nervous system by Abe and Kimura in 1996, the physiopathological role of H2S has been widely investigated in several systems such as the cardiovascular. In particular, H2S plays a pivotal role in the control of vascular tone, exhibiting mechanisms of action able to induce vasodilation: for instance, activation of potassium channels (KATP and Kv7) and inhibition of 5-phosphodiesterase (5-PDE). These findings paved the way for the research of natural and synthetic exogenous H2S-donors (i.e., molecules able to release H2S) in order to have new tools for the management of hypertension. In this scenario, some natural molecules derived from Alliaceae (i.e., garlic) and Brassicaceae (i.e., rocket or broccoli) botanical families show the profile of slow H2S-donors able to mimic the endogenous production of this gasotransmitter and therefore can be viewed as interesting potential tools for management of hypertension or pre-hypertension. In this article, the preclinical and clinical impacts of these natural H2S-donors on hypertension and vascular integrity have been reviewed in order to give a complete panorama of their potential use for the management of hypertension and related vascular diseases. [ABSTRACT FROM AUTHOR]

Obesity is currently considered a major source of morbidity, with dramatic complications on health status and life expectancy. Several studies demonstrated the positive effects of Brassicaceae vegetables on obesity and related diseases, partially attributing these beneficial properties to glucosinolates and their derivatives isothiocyanates. Recently, isothiocyanates have been described as a hydrogen sulfide (H2S)‐releasing moiety, suggesting that H2S may be at least in part responsible for the beneficial effects of Brassicaceae. In this work, the metabolic effects of an extract obtained from Eruca sativa Mill. seeds (E.S., Brassicaceae), containing high levels of glucoerucin, were evaluated in an experimental model of obesity. Male balb/c mice were fed for 10 weeks with standard (Std) diet or high fat (HF) diet supplemented with E.S. E.S. significantly contained the body weight gain in this obesity model, improving also glucose homeostasis. Interestingly, lower values of white adipose tissue mass and a significant reduction of adipocytes size were also observed. Moreover, E.S. enhanced the adipocytes metabolism, improving the citrate synthase activity and reduced triglyceride levels in mice fed with HF diet. Taken together, these results suggest that E.S. is endowed with an interesting translational and nutraceutical value in the prevention of metabolic disorders, suggesting that H2S could be a key player. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) represents the most common age‐related metabolic disorder, and its management is becoming both a health and economic issue worldwide. Moreover, chronic hyperglycemia represents one of the main risk factors for cardiovascular complications. In the last years, the emerging evidence about the role of the endogenous gasotransmitter hydrogen sulfide (H2S) in the pathogenesis and progression of T2DM led to increasing interest in the pharmacological modulation of endogenous "H2S‐system". Indeed, H2S directly contributes to the homeostatic maintenance of blood glucose levels; moreover, it improves impaired angiogenesis and endothelial dysfunction under hyperglycemic conditions. Moreover, H2S promotes significant antioxidant, anti‐inflammatory, and antiapoptotic effects, thus preventing hyperglycemia‐induced vascular damage, diabetic nephropathy, and cardiomyopathy. Therefore, H2S‐releasing molecules represent a promising strategy in both clinical management of T2DM and prevention of macro‐ and micro‐vascular complications associated to hyperglycemia. Recently, growing attention has been focused on dietary organosulfur compounds. Among them, garlic polysulfides and isothiocyanates deriving from Brassicaceae have been recognized as H2S‐donors of great pharmacological and nutraceutical interest. Therefore, a better understanding of the therapeutic potential of naturally occurring H2S‐donors may pave the way to a more rational use of these nutraceuticals in the modulation of H2S homeostasis in T2DM. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hydrogen sulfide (H2 S)-releasing agents are viewed as potential antihypertensive drugs. Recently, natural isothiocyanates emerged as original H2 S-donor agents. Among them, erucin, present in some edible cruciferous plants, shows suitable H2 S-releasing properties and features of "druggability." The aim of this work was to investigate the erucin-mediated release of H2 S inside vascular cells, its vasorelaxing effects, and activity on BP of normo and hypertensive animals.Experimental Approach: Intracellular H2 S-release and the hyperpolarizing effect of erucin were tested using fluorescent dye, in human aortic smooth muscle cells (HASMCs). Its direct vasorelaxing effect and ability to inhibit noradrenaline-induced vasoconstriction were evaluated on endothelium-intact or -denuded rat aortic rings. Its vasodilator properties were tested in coronary arteries using Langendorff-perfused rat hearts. Finally, erucin's antihypertensive activity was evaluated in vivo in normotensive and spontaneously hypertensive rats (SHRs) by recording systolic BP using the tail-cuff method.Key Results: Erucin induced the release of H2 S inside HASMCs. Moreover, erucin hyperpolarized the membrane of HASMCs membrane in a concentration-dependent manner. It induced vasodilatation of rat aortic rings, in endothelium-denuded vessels. This effect was further improved by the presence of endothelial NO. When pre-incubated with rat aortic rings, erucin induced concentration-dependent inhibition of noradrenaline-induced vasoconstriction. Erucin did not affect basal coronary flow but restored the flow to normal in pre-contracted coronary vessels. Finally, in vivo, erucin decreased systolic BP in SHRs by about 25%, and restored the BP to values observed in normotensive rats.Conclusions and Implications: Erucin is an H2 S donor endowed with vasorelaxing and antihypertensive effects.Linked Articles: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc. [ABSTRACT FROM AUTHOR]